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Abstract SUMMARY AND CONCLUSION Sepsis in newborns is a common fatal disorder affecting 1.1-2.7% of all newborns. In spite of extensive research and development in understanding and treatment of neonatal sepsis, sepsis continues to be a major source of morbidity and mortality in the neonatal population. Neonatal sepsis (NS) remains a diagnostic burden problem by showing minimal initial symptoms of subtle character, nonspecific manifestations, and diagnostic pitfalls. The clinical course can be fulminate and fatal if treatment is not commenced promptly. It is therefore crucial to establish early diagnosis and initiate adequate therapy. The rapid diagnosis and management of infection are heavily dependent upon clinical assessment. Blood culture may take up to 7 days for results and may be inconclusive, thus there is an urgent need for a specific marker to aid in diagnosis of sepsis and in prognosis. Pro-adrenomedullin (pro-ADM) is a kind of ”hormokine” that encompasses the cytokine-like behavior of hormones during inflammation and infections. Adrenomedullin (ADM) is a 52-amino-acid peptide produced by the adrenal medulla. ADM is produced during Summary 156 physiological stress and has various functions including vasodilation and anti-inflammatory and antimicrobial effects. Plasma ADM concentration and ADM gene expression increases in patients with sepsis. However, ADM is rapidly cleared from the circulation, making measurements unreliable. Therefore, instead of ADM, serum quantification of the mid-regional fragment of pro-ADM has been measured. In this regard, the present study aimed to evaluate the clinical utility of serum Pro-ADM in severity and prognosis of neonatal sepsis at Ain Shams University Hospital`s NICUs and comparing it with conventional markers of infection in newborns. This study was conducted at the Department of Clinical Pathology and Department of Pediatrics at Ain Shams University Hospitals on ninety (90) neonates divided into 3 groups; 30 clinically suspected sepsis neonates as group I, 30 neonates with proved sepsis as group II, in addition to 30 healthy control neonates as group III. All patients in the study were subjected to adequate history taking, full clinical examination, CBC, CRP, blood culture, total bilirubin, ALT, AST, creatinine, BUN and Summary 157 serum pro-adrenomedullin (pro-ADM) assay by ELISA technique. In our study we found that neonates with neonatal sepsis had their serum pro-ADM levels significantly higher than those of the control group. Also there were a highly significant difference as regard pro-ADM in proved sepsis group than clinically suspected sepsis group. There was a significant positive correlation between serum pro-ADM level proved sepsis group with CRP and sepsis score. In addition, ROC curve analysis revealed that the diagnostic sensitivity, specificity, PPV, NPV, efficacy and AUC of pro-ADM were 66.7%, 63.3%, 64.5%, 65.5%, 65% and 0.622 respectivly at a cut off value of 95 ng/L in discriminating between proved sepsis group and clinically suspected sepsis group. Our study revealed that circulating levels of pro-ADM vary to a much greater extent between health and disease with significantly higher levels in patients with sepsis who did not survive than in survivors .Thus,we concluded that pro-ADM can be used as predictor of outcome in sepsis. In conclusion, the results of our study indicated clearly that pro-ADM levels are higher in patients with either proved sepsis or clinically suspected sepsis as compared with healthy controls. As this new biomarker show high concentration in the presence of sepsis, it paves the way for promising applications in the prognosis and early diagnosis of sepsis to complement previously known markers such as WBCs count, CRP and PCT. |